RNA recognition by double-stranded RNA binding domains: a matter of shape and sequence

Abstract

The double-stranded RNA binding domain (dsRBD) is a small protein domain of 65-70 amino acids adopting an αβββα fold, whose central property is to bind to double-stranded RNA (dsRNA). This domain is present in proteins implicated in many aspects of cellular life, including antiviral response, RNA editing, RNA processing, RNA transport and, last but not least, RNA silencing. Even though proteins containing dsRBDs can bind to very specific dsRNA targets in vivo, the binding of dsRBDs to dsRNA is commonly believed to be shape-dependent rather than sequence-specific. Interestingly, recent structural information on dsRNA recognition by dsRBDs opens the possibility that this domain performs a direct readout of RNA sequence in the minor groove, allowing a global reconsideration of the principles describing dsRNA recognition by dsRBDs. We review in this article the current structural and molecular knowledge on dsRBDs, emphasizing the intricate relationship between the amino acid sequence, the structure of the domain and its RNA recognition capacity. We especially focus on the molecular determinants of dsRNA recognition and describe how sequence discrimination can be achieved by this type of domain.

The human RBPome: From genes and proteins to human disease

“…The domain distribution of this catalogue ( Figure 1B) illustrates the presence of various known and well-studied RNA binding domains like RRM (RNA recognition motif) [30], K-homology (KH) [31,32], DEAD/DEAH box [33], dsrm [34], WD40 [35] in addition to unclassified domains like the Pkinase domain of EIF2AK2 that auto phosphorylates upon binding of RNA to the dsRBD domain of EIF2AK2 [36,37]. Also notable is the Calponin homology (CH) domain found in both cytoskeletal and signalling proteins [38].…”

RNA-binding protein DUS16 plays an essential role in primary miRNA processing in the unicellular alga Chlamydomonas reinhardtii

“…1 A and B and Fig. S1) (42)(43)(44)(45). To verify the impairment of miR9897-3p-mediated silencing in dus16-1, we measured the abundance of the intact gluc Chlamydomonas expressing DUS16-Venus in a dus16-1 background (DUS16-Venus, strain #1 and #2) and wild-type cells expressing Venus (Venus, strain #3 and #4) were examined by confocal microscopy.…”

Functions of double-stranded RNA-binding domains in nucleocytoplasmic transport

“…1A). 4,12 The second dsRBD of XlrbpA forms the prototype of canonical dsRBDs with the 2 a-helices packed against the 3-stranded anti-parallel b-sheet. 13,14 In addition, structures of dsRBDs in complex with dsRNA substrates revealed the canonical mode of RNA recognition by dsRBDs.…”

“…1,2,18 In addition to this early description, it became clear that some dsRBDs display a pronounced preference for stem-loop structures, with the loop being often a primary determinant of RNA substrate recognition, 8,15,17,19 and that some dsRBDs perform a base-specific readout in the minor-groove via sequence specific contacts involving helix a1 and the b1-b2 loop. 4,7,20 One should therefore be aware that, beyond the A-form RNA helix, dsRBDs are sensitive to additional RNA features, such as apical loops, base-pair mismatches, bulges and nucleotide sequence.…”

“…This type of protein-RNA interaction regulates diverse biological processes such as response to viral infection, gene silencing through RNA interference pathways, RNA processing, regulation of translation, mRNA editing, RNA export and mRNA localization. [1][2][3][4] Proteins interacting with dsRNA often sense the double-helix RNA structure through one or multiple doublestranded RNA-binding domains (dsRBDs). The dsRBD (also referred to as dsRBM for double-stranded RNA-binding motif) is a conserved protein domain of approximately 65-70 amino acids in length, which binds double-stranded or highly structured RNAs.…”